Neuroimmunomodulation in Major Depressive Disorder: Focus on Caspase 1, Inducible Nitric Oxide Synthase, and Interferon-Gamma

Antonio Inserra, Claudio Alberto Mastronardi, Geraint Rogers, Julio Licinio, Ma Li Wong

Research output: Contribution to journalReview article

13 Citations (Scopus)


Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its incidence is expected to increase. Despite tremendous efforts to understand its underlying biological mechanisms, MDD pathophysiology remains elusive and pharmacotherapy outcomes are still far from ideal. Low-grade chronic inflammation seems to play a key role in mediating the interface between psychological stress, depressive symptomatology, altered intestinal microbiology, and MDD onset. We review the available pre-clinical and clinical evidence of an involvement of pro-inflammatory pathways in the pathogenesis, treatment, and remission of MDD. We focus on caspase 1, inducible nitric oxide synthase, and interferon gamma, three inflammatory systems dysregulated in MDD. Treatment strategies aiming at targeting such pathways alone or in combination with classical therapies could prove valuable in MDD. Further studies are needed to assess the safety and efficacy of immune modulation in MDD and other psychiatric disorders with neuroinflammatory components.

Original languageEnglish
Pages (from-to)4288-4305
Number of pages18
JournalMolecular Neurobiology
Issue number6
Publication statusPublished - 1 Jun 2019


  • Caspase 1
  • Gut microbiome
  • Inducible nitric oxide synthase
  • Inflammasome
  • Inflammation
  • Interferon gamma
  • Interleukin 1
  • MDD
  • Major depressive disorder
  • Neuroinflammation
  • T-helper 1 (Th1)

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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